Molecularly targeted cancer combination therapy with near-infrared photoimmunotherapy and near-infrared photorelease with duocarmycin–antibody conjugate

Tadanobu Nagaya, Alexander P. Gorka, Roger R. Nani, Shuhei Okuyama, Fusa Ogata, Yasuhiro Maruoka, Peter L. Choyke, Martin J. Schnermann, Hisataka Kobayashi

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that uses an antibody–photoabsorber conjugate (APC). However, the effect of NIR-PIT can be enhanced when combined with other therapies. NIR photocaging groups, based on the heptamethine cyanine scaffold, have been developed to release bioactive molecules near targets after exposure to light. Here, we investigated the combination of NIR-PIT using panitumumab–IR700 (pan-IR700) and the NIR-releasing compound, CyEt–panitumumab–duocarmycin (CyEt-Pan-Duo). Both pan-IR700 and CyEt-Pan-Duo showed specific binding to the EGFR-expressing MDAMB468 cell line in vitro. In in vivo studies, additional injection of CyEt-Pan-Duo immediately after NIR light exposure resulted in high tumor accumulation and high tumor–background ratio. To evaluate the effects of combination therapy in vivo, tumor-bearing mice were separated into 4 groups: (i) control, (ii) NIR-PIT, (iii) NIR-release, (iv) combination of NIR-PIT and NIR-release. Tumor growth was significantly inhibited in all treatment groups compared with the control group (P < 0.05), and significantly prolonged survival was achieved (P < 0.05 vs. control). The greatest therapeutic effect was shown with NIR-PIT and NIR-release combination therapy. In conclusion, combination therapy of NIR-PIT and NIR-release enhanced the therapeutic effects compared with either NIR-PIT or NIR-release therapy alone.

Original languageEnglish
Pages (from-to)661-670
Number of pages10
JournalMolecular cancer therapeutics
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 1 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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